Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo |
| |
Authors: | Jing Lu Junye Miao Tao Su Ying Liu Rongqiao He |
| |
Institution: | 1. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;2. Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China;3. University of Chinese Academy of Sciences, Beijing 100049, China;4. The University of Queensland, Queensland Brain Institute, Qld 4072, Australia |
| |
Abstract: | BackgroundChronic formaldehyde exposure leads to memory impairment and abnormal elevation of endogenous formaldehyde has been found in the brains of Alzheimer's disease (AD) patients. Hyperphosphorylated Tau protein with subsequent aggregates as neurofibrillary tangles (NFTs) is one of the typical pathological characteristics in AD brains. The mechanism underlying abnormally elevated concentrations of endogenous formaldehyde that induce Tau hyperphosphorylation is unknown.MethodsN2a cells and mice were treated with formaldehyde for different time points, then Western blotting and immunocytochemistry were utilized to determine the phosphorylation and polymerization of Tau protein. HPLC was used to detect the concentration of formaldehyde in cell media.ResultsUnder formaldehyde stress, Tau became hyperphosphorylated, not only in the cytoplasm, but also in the nucleus of neuroblastoma (N2a) cells, and mouse brains. Polymers of cellular phospho-Tau were also detected. Significant accumulation of glycogen synthase kinase-3β (GSK-3β) in the nucleus of N2a and mouse brain cells, and elevation of its phosphorylation at Y216, was observed under formaldehyde stress. Formaldehyde-induced Tau hyperphosphorylation was blocked in the presence of LiCl and CT99021, inhibitors of GSK-3β, and by RNAi interference.ConclusionsFormaldehyde, which may cause age-related memory loss, can act as a factor triggering Tau hyperphosphorylation via GSK-3β catalysis and induces polymerization of Tau.General significanceInvestigation of formaldehyde-induced Tau hyperphosphorylation may provide novel insights into mechanisms underlying tauopathies. |
| |
Keywords: | AD Alzheimer's disease GSK-3β glycogen synthase kinase-3β NFTs neurofibrillary tangles PHFs paired helical filaments FA formaldehyde pTau phosphorylated Tau |
本文献已被 ScienceDirect 等数据库收录! |
|